Major depressive disorder (MDD) is one of the most prevalent and debilitating mental disorders in the world. Clinical trials recruiting depressed individuals are instrumental in the development and evaluation of effective treatments for depression. The safety of participants in clinical trials is overseen by the Institutional review boards (IRBs). Concerns about abilities of people with depression to make an informed decision about research participation have been an ongoing source of debate. Many, including IRB reviewers, presume that mental disorders compromise decision-making. However, empirical data regarding decision-making abilities of depressed persons in research context are scant. IRBs must therefore make recommendations based on accepted wisdom rather than empirical evidence. This likely results in the variability in recommendations of IRBs regarding the appropriate level of protection of depressed individuals. Whereas instruments assessing the individuals' capacity to give informed consent exist, they can only determine whether a person knows how to make a decision, but not whether a decision is consistent with a person's preferences and is in his or her best interest. Thus, the question of whether depression affects the quality of decisions remains unaddressed. The proposed project aims to provide data that will ultimately help those entrusted with the well-being of research participants to select appropriate degree of safeguards for depressed individuals enrolling in research. This will be accomplished by using tools from health economics and health decision-making to understand the influence of MDD on the evaluation of risks and benefits of hypothetical clinical trials. Decisions made by depressed individuals will be examined for consistency with their preferences for better health states, and compared to decisions made by individuals with chronic pain (a comparably disabling non-psychiatric condition), with comorbid MDD and pain, and to decisions of healthy controls. This research is responsive to NIMH Strategic Objectives 3 and 4. Results of this study have the potential to streamline research involving depressed persons by providing major stakeholders the data which either supports the need for additional protection, or determines that no additional safeguards are necessary. It may shed light on the difficulties depressed individuals experience with decision-making, thereby providing a new focus of interventions. This project describes a five-year program to develop an academic career in psychology under the mentorship of Dr. Laura Dunn, who has extensive experience in bioethics and issues related to capacity to provide informed consent. In addition, Dr. Ricardo Muqoz, a co-mentor, will provide guidance on aspects of the project related to depression, and Dr. Jonathan Baron, a consultant, will provide assistance and training in decision-making. Ultimately, this project will allow the establishment of a line of inquiry combining psychopathology and decision-making in a mutually informative relationship; the scientific development afforded by this award will provide the skills necessary to become a successful independent investigator.